Treatment Outcome of Locally Advanced Non-small Cell Lung Cancer Patients Who Received Concurrent Chemoradiotherapy with Weekly Paclitaxel

Paclitaxel 매주 투여 및 방사선치료 동시요법을 받은 국소진행성 비소세포폐암 환자들의 치료 결과

  • Kim, Su-Zy (Lung Cancer Center, St. Vincent's Hospital, Departments of Radiation Oncology, The Catholic University of Korea College of Medicine) ;
  • Shim, Byoung-Yong (Lung Cancer Center, St. Vincent's Hospital, Departments of Internal Medicine, The Catholic University of Korea College of Medicine) ;
  • Kim, Chi-Hong (Lung Cancer Center, St. Vincent's Hospital, Departments of Internal Medicine, The Catholic University of Korea College of Medicine) ;
  • Song, So-Hyang (Lung Cancer Center, St. Vincent's Hospital, Departments of Internal Medicine, The Catholic University of Korea College of Medicine) ;
  • Ahn, Meyung-Im (Lung Cancer Center, St. Vincent's Hospital, Departments of Diagnostic Radiology, The Catholic University of Korea College of Medicine) ;
  • Cho, Deog-Gon (Lung Cancer Center, St. Vincent's Hospital, Departments of Chest Surgery, The Catholic University of Korea College of Medicine) ;
  • Cho, Kyu-Do (Lung Cancer Center, St. Vincent's Hospital, Departments of Chest Surgery, The Catholic University of Korea College of Medicine) ;
  • Yoo, Jin-Young (Lung Cancer Center, St. Vincent's Hospital, Departments of Pathology, The Catholic University of Korea College of Medicine) ;
  • Kim, Hoon-Kyo (Lung Cancer Center, St. Vincent's Hospital, Departments of Internal Medicine, The Catholic University of Korea College of Medicine) ;
  • Kim, Sung-Whan (Lung Cancer Center, St. Vincent's Hospital, Departments of Radiation Oncology, The Catholic University of Korea College of Medicine)
  • 김수지 (성빈센트병원 폐암센터, 가톨릭대학교 의과대학 방사선종양학교실) ;
  • 심병용 (성빈센트병원 폐암센터, 가톨릭대학교 의과대학 내과학교실) ;
  • 김치홍 (성빈센트병원 폐암센터, 가톨릭대학교 의과대학 내과학교실) ;
  • 송소향 (성빈센트병원 폐암센터, 가톨릭대학교 의과대학 내과학교실) ;
  • 안명임 (성빈센트병원 폐암센터, 가톨릭대학교 의과대학 진단방사선학교실) ;
  • 조덕곤 (성빈센트병원 폐암센터, 가톨릭대학교 의과대학 흉부외과학교실) ;
  • 조규도 (성빈센트병원 폐암센터, 가톨릭대학교 의과대학 흉부회과학교실) ;
  • 유진영 (성빈센트병원 폐암센터, 가톨릭대학교 의과대학 병리학교실) ;
  • 김훈교 (성빈센트병원 폐암센터, 가톨릭대학교 의과대학 내과학교실) ;
  • 김성환 (성빈센트병원 폐암센터, 가톨릭대학교 의과대학 방사선종양학교실)
  • Published : 2006.12.31

Abstract

$\underline{Purpose}$: To analyze the response, toxicity, patterns of failure and survival rate of patients with locally advanced non-small cell lung cancer who were treated with concurrent chemoradiotherapy with weekly paclitaxel. $\underline{Materials\;and\;Methods}$: Twenty-three patients with locally advanced non-small cell lung cancer patients who received radical chemoradiotherapy from October 1999 to September 2004 were included in this retrospective study. Patients received total $55.4{\sim}64.8$ (median 64.8) Gy (daily 1.8 Gy per fraction, 5 days per weeks) over $7{\sim}8$ weeks. 50 or $60\;mg/m^2$ of paclitaxel was administered on day 1, 8, 15, 22, 29 and 36 of radiotherapy. Four weeks after the concurrent chemoradiotherapy, three cycles of consolidation chemotherapy consisted of paclitaxel $135\;mg/m^2$ and cisplatin $75\;mg/m^2$ was administered every 3 weeks. $\underline{Results}$: Of the 23 patients, 3 patients refused to receive the treatment during the concurrent chemoradiotherapy. One patient died of bacterial pneumonia during the concurrent chemoradiotherapy. Grade 2 radiation esophagitis was observed in 4 patients (17%). Sixteen patients received consolidation chemotherapy. During the consolidation chemotherapy, 8 patients (50%) experienced grade 3 or 4 neutropenia and one of those patients died of neutropenic sepsis. Overall response rate for 20 evaluable patients was 90% including 4 complete responses (20%) and 14 partial responses (70%). Among 18 responders, 9 had local failure, 3 had local and distant failure and 2 had distant failure only. Median progression-free survival time was 9.5 months and 2-year progression-free survival rate was 19%. Eleven patients received second-line or third-line chemotherapy after the treatment failure. The median overall survival time was 21 months. 2-year and 5-year survival rate were 43% and 33%, respectively. Age, performance status, tumor size were significant prognostic factors for progression-free survival. $\underline{Conclusion}$: Concurrent chemoradiotherapy with weekly paclitaxel revealed high response rate and low toxicity rate. But local failure occurred frequently after the remission and large tumor size was a poor prognostic factor. Further investigations are needed to improve the local control.

목 적: 국소진행성 비소세포폐암 환자에 대한 매주 paclitaxel 항암화학요법과 방사선치료 동시 요법의 안정성과 효과를 알아보고 재발 양상 및 생존율을 분석하고자 하였다. 대상 및 방법: 1999년 10월부터 2004년 9월까지 국소진행성 비소세포폐암으로 진단받고 근치적 목적으로 항암화학방사선 동시요법을 시행 받은 환자 23명을 대상으로 후향적 분석을 시행하였다. 방사선치료는 일일 1회 1.8 Gy씩 주5회 분할 조사하여 $7{\sim}8$주에 걸쳐 총 선량 $55.8{\sim}64.8$ (median 64.8) Gy를 조사하였다. 항암화학요법은 매주 paclitaxel 50 또는 $60\;mg/m^2$ 용량으로 방사선치료 1일, 8일, 15일, 22일, 29일 36일째에 투여하였다. 항암화학방사선 동시요법을 마친 4주 후부터 paclitaxel $135\;mg/m^2$와 cisplatin $75\;mg/m^2$ 용량으로 3주 간격으로 3주기의 공고 항암화학요법을 추가 시행하였다. 결 과: 동시 항암화학방사선요법을 시행받은 23명의 환자 중 3명이 도중에 환자 임의로 치료를 중단하였고 1명이 5,580 cGy까지 방사선치료를 시행 받고 세균성 폐렴으로 사망하였다. 주된 급성 부작용은 방사선 식도염으로 4명(17%)의 환자에서 2도의 식도염이 관찰되었으며 3도 이상의 부작용은 관찰되지 않았다. 16명의 환자가 추가 공고 항암화학요법을 시행 받았으며 공고 항암화학요법 중의 급성 부작용으로 3도 이상의 호중구 감소증이 8명(50%)의 환자에서 관찰되었으며 그중 한 명은 패혈증으로 사망하였다. 동시 항암화학방사선요법을 끝까지 시행 받은 20명의 환자에서 치료에 대한 반응을 조사할 수 있었으며 완전 관해 4명(20%), 부분 관해 14명(70%)으로 전체 관해율은 90%이었다. 관해를 보인 환자들 중 추적 관찰이 가능했던 16명 중 14명에서 재발이 확인되었고 국소 재발이 9명(56%), 국소 재발과 원격 전이가 3명(19%), 원격 전이가 2명(13%)이었다. 동시 항암화학방사선요법을 끝까지 시행받은 환자들에서의 무진행 생존 기간의 중앙값은 9.5개월이었으며, 2년 무진행 생존율은 18%이었다. 재발된 환자 중 11명에서 2차(second-line) 또는 3차(third-line) 항암화학요법이 시행되었다. 전체 환자 23명의 중앙 생존 기간은 21개월, 2년 및 5년 생존율은 각각 43%, 33%였다. 다변량 분석을 시행했을 때 환자의 나이, 수행 능력, 종양의 크기는 무진행 생존율에 영향을 주는 유의한 예후 인자로 나타났다. 결 론: 국소진행성 비소세포폐암 환자에서 paclitaxel 매주 투여 항암화학요법과 방사선치료 동시요법은 안전하고 종양의 관해율도 높았다. 그러나 국소 재발률이 높고 특히 종양의 크기가 큰 환자에서 예후가 나쁜 것을 알 수 있었다. 따라서 향후 부작용은 증가시키지 않으면서 국소제어율을 향상시키기 위한 노력이 필요하다.

Keywords

References

  1. Petrovich Z, Stanley K, Cox JD, Paig C. Radiotherapy in the management of locally advanced lung cancer of all cell types: final report of randomized trial. Cancer 1981;48:1335-1340 https://doi.org/10.1002/1097-0142(19810915)48:6<1335::AID-CNCR2820480614>3.0.CO;2-S
  2. Johnson DH, Einhorn LH, Bartolucci A, et al. Thoracic radiotherapy does not prolong survival in patients with locally advanced, unresectable non-small cell lung cancer. Ann Intern Med 1990;113:33-38 https://doi.org/10.7326/0003-4819-113-1-33
  3. Cox JD, Pajak TF, Herskovic A, Urtasun R, Podolsky WJ, Seydel HG. Five-year survival after hyperfractionated radiation therapy for non-small cell carcinoma of the lung (NSCCL): results of RTOG protocol 81-08. Am J Clin Oncol 1991;14:280-284 https://doi.org/10.1097/00000421-199108000-00002
  4. Dillman RO, Herndon J, Seagren SL, Eaton WL Jr, Green MR. Improved survival in stage III non-small-cell lung cancer: seven-year follow-up of cancer and leukemia group B (CALGB) 8433 trial. J Natl Cancer Inst 1996;88:1210-1215 https://doi.org/10.1093/jnci/88.17.1210
  5. Sause W, Kolesar P, Taylor S IV, et al. Final results of phase III trial in regionally advanced unresectable non-small cell lung cancer: Radiation Therapy Oncology Group, Eastern Cooperative Oncology Group, and Southwest Oncology Group. Chest 2000;117:358-364 https://doi.org/10.1378/chest.117.2.358
  6. Furuse K, Fukuoka M, Kawahara M, et al. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, vindesine, and cisplatin in unresectable stage III non-small-cell lung cancer. J Clin Oncol 1999;17:2692-2699 https://doi.org/10.1200/JCO.1999.17.9.2692
  7. Curran WJ, Scott C, Langer C, et al. Phase III comparison of sequential vs. concurrent chemoradiation for patients with unresected stage III non-small cell lung cancer (NSCLC): initial report of Radiation Therapy Oncology Group (RTOG) 9410 [Abstract]. Proc Am Soc Clin Oncol 2000;19:1819
  8. Murphy WK, Fossella FV, Winn RJ, et al. Phase II study of taxol in patients with untreated advanced non-small-cell lung cancer. J Natl Cancer Inst 1993;85:384-388 https://doi.org/10.1093/jnci/85.5.384
  9. Chang AY, Kim K, Glick J, Anderson T, Karp D, Johnson D. Phase II study of taxol, merbarone and piroxantrone in stage IV non-small-cell lung cancer: The Eastern Cooperative Oncology Group Results. J Natl Cancer Inst 1993;85:388-394 https://doi.org/10.1093/jnci/85.5.388
  10. Milross CG, Mason KA, Hunter NR, Chung WK, Peters LJ, Milas L. Relationship of mitotic arrest and apoptosis to antitumor effect of paclitaxel. J Natl Cancer Inst 1996;88: 1308-1314 https://doi.org/10.1093/jnci/88.18.1308
  11. Milas L, Hunter NR, Mason KA, Milross CG, Saito Y, Peters LJ. Role of reoxygenation in induction of enhancement of tumor radioresponse by paclitaxel. Cancer Res 1995; 55:3564-3568
  12. NCI CTC v.2.0. http://ctep.cancer.gov/reporting/ctc.html
  13. Herrmann T, Knorr A, Dorner K. The RTOG/EORTC classification criteria for early and late radiation reactions. Radiobiol Radiother (Berl) 1987;28:519-528
  14. Choy H, Akerley W, Safran H, et al. Phase I trial of outpatient weekly paclitaxel and concurrent radiation therapy for advanced non-small cell lung cancer. J Clin Oncol 1994;12:2682-2686 https://doi.org/10.1200/JCO.1994.12.12.2682
  15. Choy H, Safran H, Akerley W, Graziano SL, Bogart JA, Cole BF. Phase II trial of weekly paclitaxel and concurrent radiation therapy for locally advanced non-small cell lung cancer. Clin Cancer Res 1998;4:1931-1936
  16. Gandara DR, Chansky K, Albain KS, et al. Consolidation docetaxel after concurrent chemoradiotherapy in stage IIIB non-small-cell lung cancer: phase II Southwest Oncology Group Study S9504. J Clin Oncol 2003;21:2004-2010 https://doi.org/10.1200/JCO.2003.04.197
  17. Kelly K, Gaspar LE, Chansky KS, et al. SWOG 0023: a randomized phase III trial of cisplatin/etoposide (PE) plus radiation therapy followed by consolidation docetaxel then maintenance therapy with gefitinib or placebo in patients with locally advanced unresectable stage III non small cell lung cancer. Lung Cancer. 2005;49(suppl 2):S64
  18. Bae S, Kim KC, Lee S, et al. Efficacy of weekly paclitaxel and concurrent radiation therapy for locally advanced non- small cell lung cancer. Korean J Med 2005;69:379-386
  19. Bae KW, Song TH, Yang JY, et al. Concurrent chemoradiation with weekly paclitaxel in locally advanced non-small cell lung cancer. Tuberc Respir Dis 2004;57:351-357 https://doi.org/10.4046/trd.2004.57.4.351
  20. Kim YS, Yoon SM, Choi EK, et al. Phase II study of radiotherapy with three-dimensional conformal boost concurrent with paclitaxel and cisplatin for stage III non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 2005;62:76-81 https://doi.org/10.1016/j.ijrobp.2004.09.038
  21. Shim BY, Kim CH, Song SH, et al. The safety and efficacy of second-line single docetaxel (75 mg/$m^2$) therapy in advanced non-small cell lung cancer patients who were previously treated with platinum-based chemotherapy. Cancer Res Treat 2005;37:339-343 https://doi.org/10.4143/crt.2005.37.6.339